Despite considerable recent progress, an HIV vaccine that is capable of inducing immune responses that can prevent or control HIV infection has not yet been achieved. Delivery of antigen in a manner that induces effective, antigen-specific immunity is a critical challenge in a vaccine design. Optimal antigen presentation is mediated by professional Antigen Presenting Cells (APCs) capable of taking-up, processing, and presenting antigen to T-cells in the context of co-stimulatory signals required for T-cell activation. The applicants believe that the development of immunization strategies to optimize antigen presentation by APCs is a rational approach to vaccine design. The studies proposed have a single specific aim - to define techniques to deliver and express genes in antigen presenting cells in human skin. The applicants plan to evaluate gene expression quantitatively and qualitatively after various methods of naked DNA delivery, with emphasis on the evaluation of gene expression in cutaneous dendritic cells. The goal of the proposed experiments proposed is to establish basic techniques for cutaneous gene delivery and for the analysis and comparison of evolving gene delivery technologies. These studies are designed to demonstrate feasibility and provide rationale for continuing development of cutaneous genetic immunization, including the initiation of clinical trials for the prevention and treatment of HIV infection.